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Potential anti-hepatocellular carcinoma properties and mechanisms of action of clerodane diterpenes isolated from Polyalthia longifolia seeds.

ABSTRACT: Diterpenes are secondary metabolites that have attracted much attention due to their potential biological activities including anti-cancer potential. The aim of the current study is to assess the anticancer potential of the six known clerodane diterpenes (1-6) isolated from Polyalthia longifolia seeds and their underlying molecular mechanisms. These compounds were evaluated for their cytotoxicity in vitro by using MTT assays. The "two-phase model" with NDEA and PB ad libitum was used for induction of HCC and sorafenib was used as the standard drug. Prophylactic studies were carried out for compounds 4/6 at both low (5 mg/kg b.w) and high (10 mg/kg b.w) doses. Based on the MTT assay results, the two best compounds, 4 and 6, were selected for in vivo studies. The results showed that treatment with compound 4/6 significantly restored the changes in biochemical parameters and liver morphology observed in (NDEA + PB)-induced HCC rats. Additionally, the docking studies showed that compound 4/6 interacted with several key proteins such as MDM2, TNF-α, FAK, thereby inhibiting these proteins and reversing the negative impacts of NDEA. In conclusion, our results suggested that compounds 4 and 6 are potential therapeutic agents for HCC, mostly due to their ability to control typical cancer pathways.

SUBMITTER: Tatipamula VB

PROVIDER: S-EPMC9166726 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Potential anti-hepatocellular carcinoma properties and mechanisms of action of clerodane diterpenes isolated from Polyalthia longifolia seeds.

Tatipamula Vinay Bharadwaj VB Thonangi Chandi Vishala CV Dakal Tikam Chand TC Vedula Girija Sastry GS Dhabhai Bhanupriya B Polimati Haritha H Akula Annapurna A Nguyen Ha Thi HT

Scientific reports 20220603 1

Diterpenes are secondary metabolites that have attracted much attention due to their potential biological activities including anti-cancer potential. The aim of the current study is to assess the anticancer potential of the six known clerodane diterpenes (1-6) isolated from Polyalthia longifolia seeds and their underlying molecular mechanisms. These compounds were evaluated for their cytotoxicity in vitro by using MTT assays. The "two-phase model" with NDEA and PB ad libitum was used for inducti ...[more]

PMID: 35661799

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Project description:The marine sponge Raspailia bouryesnaultae, collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against Herpes Simplexvirus type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge's hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (1), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene (2) with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (3), kerlinic acid methyl ester (4), annonene (5), and 6-hydroxyannonene (6). They differ in their stereochemistry, since these diterpenes are characterized by a trans ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a cis relationship (type trans/cis). The Raspailia diterpenes have a cis ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a trans relationship (type cis/trans). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC50) values lower than 25 μM. The evaluation of the potential anti-herpes activity against Herpes Simplex Virus type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound 2, since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.

Dataset Information

Potential anti-hepatocellular carcinoma properties and mechanisms of action of clerodane diterpenes isolated from Polyalthia longifolia seeds.

Publications

Potential anti-hepatocellular carcinoma properties and mechanisms of action of clerodane diterpenes isolated from Polyalthia longifolia seeds.

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